Loss of kidney function represents a catastrophic illness leading inevitably to death of the patient if untreated. Dialysis is a major therapeutic tool to replace kidney function. However, renal bone disease occurs in virtually all patients on dialysis. Today, in most patients, two major types of renal bone disease are seen: high turnover hyperparathyroid bone disease and low turnover adynamic bone disease. It is not fully understood why patients develop these abnormalities and newly developed laboratory techniques allow to study these bone changes at the cellular and molecular level. For this purpose, blood drawings and bone biopsies are needed. The proposed studies represent a comprehensive approach to study the pathogenesis of renal bone disease. Specifically, the pathogenetic role of the previously identified major factors parathyroid hormone (PTH), calcitriol and their receptors as well as newly recognized factors that are the cytokines, interleukin-1, tumor necrosis factor-alpha, interleukin-6 and its interleukin-6 soluble receptor will be evaluated. One hundred twenty patients will be studied cross-sectionally and a subgroup of 62 of these patients will be followed prospectively for one year. For analysis of bone samples, the well-established histomorphometric technique for parameters of bone structure and static and dynamic parameters of bone formation and resorption will be employed in conjunction with the newly developed and validated in situ hybridization histochemistry technique. Moreover, the association between C-terminal PTH, C-terminal PTHrP and histologic and molecular bone changes will be evaluated. The forthcoming results will improve the understanding of the pathophysiology of renal bone disease and probably other metabolic bone diseases. This should lead to the development of new therapeutic strategies to improve the long-term outcome of dialysis, a treatment modality requiring greater than $5.9 billion annually in health care cost for approximately 280,000 Americans suffering from end-stage renal failure.